The present invention relates to improved processes for the preparation of N,Nxe2x80x2-carbonyldiazoles by reaction of azolide salts with phosgene and for the preparation of azolide salts.
It is already basically known that N,Nxe2x80x2-carbonyldiazoles can be obtained if azoles are reacted with phosgene (see DE-B 10 33 210, Chem. Ber. 96, 3374 (1963), Org. Synth. Coll. Vol. IV, 201-204 (1968), and EP-A 692,476).
It is disadvantageous in all these processes that half of the azole employed is consumed as scavenger for the hydrogen chloride formed, and therefore only a maximum of 50% of the azole employed can be converted into the desired carbonyidiazole. This is a severe disadvantage, since azoles are expensive products and large azole consumption thus causes high production costs. Furthermore, the azole hydrochlorides are partially obtained in the form of a tacky precipitate, which can be separated off from the carbonyidiazole prepared only with difficulty. Finally, the azole hydrochloride formed as by-product must be disposed of, which causes additional costs.
The process for the synthesis of N,Nxe2x80x2-carbonyidiimidazole in accordance with U.S. Pat. No. 4,965,366 attempts to avoid these disadvantages by reacting imidazole with chlorotrimethylsilane in a first reaction step to give trimethylsilylimidazole. An amine (for example, 1,2-diaminoethane) is added at this step in order to scavenge the hydrogen chloride, and the resultant amine hydrochloride is filtered off and either fed to recovery of the amine or disposed of. The trimethylsilylimidazole formed in the reaction furthermore has to be purified by distillation before the further reaction. In the next step, the trimethylsilylimidazole is reacted with phosgene. In this reaction, chlorotrimethylsilane is re-formed, and can, after purification, be reused in the reaction. Disadvantages in this process are the many synthesis and purification steps and the fact that chlorotrimethylsilane is difficult to handle due to its hygroscopic and corrosive properties. In total, three assistants have to be employed for this N,N-carbonyldiimidazole synthesis, namely chlorotrimethylsilane, 1,2-diaminoethane, and sodium hydroxide solution. In addition, the amine, the imidazole, and the solvent required for the trimethylsilylimidazole synthesis have to be dried in a complex procedure.
A process has now been found for the preparation of N,Nxe2x80x2-carbonyl-diazoles of the formula (I) 
in which
X1, X2, and X3 independently of one another are each CR1 or nitrogen,
where R1 is hydrogen or C1-C6-alkyl, and
R2 is hydrogen,
or in which
X2 is as defined above, and
X1 and X3 are CR1, where the R1 of each X1 is hydrogen or C1-C6-alkyl, and the R1 of each X3, together with R2 of the same diazole ring, forms a xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94 bridge,
comprising reacting azolide salts of the formula (II) 
in which
M⊕ is an equivalent of an alkali metal or alkaline earth metal cation or a quaternary onium ion of the formula (III)
[Y R3R4R5R6]⊕xe2x80x83xe2x80x83(III),
xe2x80x83in which
Y is phosphorus or nitrogen, and
R3, R4, R5, and R6 independently of one another are each C1-C20-alkyl, phenyl, benzyl, or ethylbenzyl, and
the other symbols are as defined for the formula (I),
with phosgene in an aromatic compound or an ether as solvent.
Preferably in the formulas (I) and (II), X1 and X2, independently of one another, are CH, N, or CCH3, X3 is CH, and R2 is hydrogen, or X1 is CH, X2 is CH, N, or CCH3, and X3 is CR1, where R1 and R2 together form a xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94 bridge.
In the formula (II), M⊕ is preferably one mol of lithium, sodium, or potassium cations or xc2xd mol of magnesium cations or 1 mol of a quaternary onium ion of the formula (III), where Y is phosphorus or nitrogen and R3, R4, R5, and R6 are C1-C8-alkyl, or R3, R4, and R5 are C1-C6-alkyl and R6 is C4-C20-alkyl, phenyl, benzyl, or ethyl. In particular, M⊕ is 1 mol of lithium, sodium, or potassium cations.
Particular preference is given to the use of sodium imidazolide or potassium imidazoline or the corresponding 1,2,4-triazolides, pyrazolides, or benzimidazolides, and particular preference is given to the preparation of N,Nxe2x80x2-carbonyidiimidazole, N,Nxe2x80x2-carbonyldi(1,2,4-triazole), N,Nxe2x80x2-carbonyl-dipyrazole, or N,Nxe2x80x2-carbonyldibenzimidazole.
In the process according to the invention, from 0.25 to 0.60 mol, for example, of phosgene can be employed per mole of azolide salt of the formula (II). This amount is preferably from 0.45 to 0.55 mol.
Suitable solvents are aromatic compounds, such as benzene, toluene, xylenes, monochlorobenzene, dichlorobenzenes and trichlorobenzenes, and ethers, such as acyclic and cyclic mono- and oligoethers, for example, diethyl ether diisopropyl ether, methyl tert-butyl ether, dibutyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and dioxane. It is also possible to employ mixtures of these solvents with one another. Preference is given to 2-methyltetrahydrofuran and aromatic solvents, particularly benzene, toluene, xylenes, monochlorobenzene, dichlorobenzenes, and mixtures of these solvents. The preferred solvents can be dried in a simple manner, for example, by azeotropic distillation. A water content of the solvent of less than 0.1% is preferred.
The process according to the invention can be carried out, for example, at temperatures in the range from 10 to 120xc2x0 C. Preference is given to temperatures in the range from 20 to 110xc2x0 C., particularly those in the range from 40 to 100xc2x0 C. The reaction temperature is preferably selected at least sufficiently high that the N,Nxe2x80x2-carbonyldiazole of the formula (I) formed does not precipitate during the reaction.
Azolide salts of the formula (II) are accessible, for example, in accordance with J. Am. Chem. Soc. 102, 4182 or EP-A 352,352. However, these processes are inconvenient and complex since either reagents which are difficult to handle are required (for example sodium hydride or butyllithium) or the azolide salt must be isolated and purified. However, a particularly favorable process for the preparation of azolide salts of the formula (II) has also been found, the details of which are described below. In the process according to the invention for the preparation of N,Nxe2x80x2-carbonyldiazoles of the formula (I), azolide salts of the formula (II) that have been prepared by the process according to the invention for the preparation of azolide salts of the formula (II) are preferably employed. This has the advantage, for example, that the azolide salt of the formula (II) does not have to be isolated but instead can be employed in the form of the reaction mixture obtained in its preparation according to the invention, if desired after removal of the solvent of the formula (VII) by distillation.
It is advantageous to carry out the process according to the invention for the preparation of N,Nxe2x80x2-carbonyldiazoles in the presence of a phase-transfer catalyst. Suitable phase-transfer catalysts are, for example, those of the formulas (VIII) to (X): 
in which
R3, R4, R5, and R6 are as defined for the formula (III),
R10 in each case independently of the others is C1-C20-alkyl, phenyl, benzyl, or ethylbenzyl,
R11 independently of R10 is as defined for R10, or
R10 and R11 together form a (xe2x80x94CH2xe2x80x94)n bridge, where n is an integer from 1 to 10,
R12 is NR10R11, C1-C20-alkyl, phenyl, benzyl, orethylbenzyl, and
Zxe2x88x92 is Clxe2x88x92, Brxe2x88x92, Ixe2x88x92, OHxe2x88x92, HSO4xe2x88x92, BF4xe2x88x92, or PF6xe2x88x92.
Azoles of the formula (IV) (see below) can also be employed as phase-transfer catalysts.
Based on one mole of azolide salt of the formula (II), it is possible to include, for example, from 0.0001 to 0.2 mol, preferably from 0.001 to 0.02 mol, of a phase-transfer catalyst.
In the preparation according to the invention of N,Nxe2x80x2-carbonyldiazoles, the second reaction product formed is a chloride of the formula
M+Clxe2x88x92xe2x80x83xe2x80x83(XI)
in which M+ is as defined for the formula (II). This chloride precipitates during the preparation of N,N-carbonyldiazole. The reaction mixture present after the reaction can be worked up, for example, by first separating off the chloride formed, for example, by filtration or siphoning-off the liquid constituents and isolating the prepared N,Nxe2x80x2-carbonyldiazole from the filtrate or the siphoned-off liquid either by cooling to from +40 to xe2x88x9270xc2x0 C., preferably to from +25 to xe2x88x9220xc2x0 C., but not lower than 5xc2x0 C. above the solidification point of the solvent used, and filtering off the product that crystallizes out during this operation or stripping off or distilling off the volatile constituents, thereby obtaining the product in solid form.
The preparation according to the invention of N,Nxe2x80x2-carbonyldiazoles has the advantage that all the azole or azolide salt employed is available for the formation of N,Nxe2x80x2-carbonyidiazole and half is not converted into azole hydrochloride. The yields of N,Nxe2x80x2-carbonyidiazole are approximately twice as high as in the direct reaction of azoles with phosgene. Even if phosgene is employed in substoichiometric amounts, a cleaner N,Nxe2x80x2-carbonyldiazole is obtained, since unreacted azolide salts are only sparingly soluble in the reaction mixture, in contrast to azoles, and, if they are present therein, are removed from the reaction mixture together with the chloride of the formula (XI). The precise stoichiometric metering of phosgene that is necessary in the direct reaction of azole with phosgene is superfluous in the process according to the invention since product contamination with unreacted azole starting material does not occur.
The present invention furthermore relates to a process for the preparation of azolide salts of the formula (II) comprising reacting an azole of the formula (IV) 
in which the symbols used are as defined for the formula (I), with a compound of the formula (V) or of the formula (VI)
Mxe2x80x2R7 xe2x80x83xe2x80x83(V)
or
MgR8Zxe2x80x2xe2x80x83xe2x80x83(VI),
in which
Mxe2x80x2 is an equivalent of an alkali metal or alkaline earth metal but is not a quaternary onium ion of the formula (III),
R7 is OR9, N(R9)2, or xc2xd CO3, where R9 is H, C1-C6-alkyl, or phenyl,
R8 is C1-C6-alkyl or phenyl, and
Zxe2x80x2 is Cl, Br, or I,
in a solvent.
In the formula (IV), the symbols used preferably have the preferred definitions indicated for the formula (I). In the formula (V), Mxe2x80x2 is preferably lithium, sodium, or potassium, and R7 is preferably OR9, where R9 is hydrogen or methyl.
In the formula (VI), R8 is preferably methyl, ethyl, or phenyl, and Zxe2x80x2 is preferably chlorine or bromine.
The solvent can be, for example, one of the solvents mentioned above for the carbonyldiazole synthesis or mixtures thereof with a solvent of the formula (VII)
HR7 xe2x80x83xe2x80x83(VII),
in which R7 is as defined for the formula (V) but cannot be xc2xd CO3.
If solvents of the formula (VII) are present after the azolide salt preparation, they are distilled off before the reaction with phosgene to give N,Nxe2x80x2-carbonyldiazoles of the formula (I).
In preferred embodiments of the process according to the invention for the preparation of azolide salts of the formula (II), the compound of the formula (V) employed is lithium hydroxide, sodium hydroxide, or potassium hydroxide, and the solvent employed is water mixed with chlorobenzene, toluene, or xylene, and the water that is introduced and formed is removed by azeotropic distillation, or the compound of the formula (V) employed is sodium methoxide and the solvent employed is methanol mixed with chlorobenzene or xylene, and the methanol that is introduced and formed is removed by distillation.
The preferred embodiments of the process according to the invention for the preparation of azolide salts of the formula (II) are particularly advantageous over the processes known from the literature since the reaction mixtures that then form, which have been freed from water and methanol, can be employed directly in the process for the preparation of N,Nxe2x80x2-carbonyidiazoles of the formula (I), and the separation, work-up, purification, and drying of the azolide salts of the formula (II) are superfluous. In addition, reagents which are expensive and can only be handled with difficulty are generally not required.
The following examples further illustrate details for the process of this invention. The invention, which is set forth in the foregoing disclosure, is not to be limited either in spirit or scope by these examples. Those skilled in the art will readily understand that known variations of the conditions of the following procedures can be used. Unless otherwise noted, all temperatures are degrees Celsius and all percentages are percentages by weight.